tbuckley/cabot-search huggingface dataset:
Outcome analysis of immunotherapy and possible prognostic role of pretreatment neutrophil-lymphocyte ratio in lung cancer: An Appalachian study.
Authors: Vivek Yadala, Yury Kachynski, Ihab Tahboub, Abraham Titus, Jai Kumar Khatri, Bhavana Vemula, Madhulika Urella, Kelsey Marshall, Mina Shenouda, Muhammad Omer Jamil, Maria Tria Tirona
Journal: Journal of Clinical Oncology (2023)

e21053 Background: Immune checkpoint inhibitors (ICI) have revolutionized the treatment of lung cancer resulting in better survival benefits. We are reporting outcome analysis of lung cancer patients treated with ICI in our institution. Methods: We performed retrospective chart review of lung cancer patients treated with ICI at our institution between June 2016 and March 2022. Results: A total of 289 patients were identified- 241 had non-small cell lung cancer (NSCLC) and 48 had small cell lung cancer (SCLC). A total of 109 patients (37.7%) developed immunotherapy related adverse events (IRAE): 92 (38.1%) with NSCLC and 17 (35.4%) with SCLC. Average time to develop IRAE was 3 months in both NSCLC and SCLC. IRAE grades 1,2,3,4 were noted in 33%, 20%, 15%, 31% patients respectively. 34 of 63 (53%) patients who received Ipilimumab-Nivolumab developed more IRAE than any other ICI with fatigue and dermatitis being the most common IRAE associated with this ICI. 79 of 183 (43%) patients who received RT developed IRAE (p = 0.012). Median overall survival (OS) for NSCLC was 35 months, 41 months, 27 months, 15 months for stages 1,2,3,4, respectively (p = 0.03). Median OS for extensive stage SCLC was 14.6 months. Median OS for NSCLC with and without IRAE was 30 and 23 months, respectively (p = 0.02). Median OS for SCLC with and without IRAE was 16.7 and 16.2 months, respectively (p = 0.5). Median OS for NSCLC when steroids were used to treat IRAE was 25 months, and 63 months if no steroids were used (p = 0.027). Better median overall survival rate was noted in patients with low Neutrophil-Lymphocyte ratio (defined as NLR &lt; 5) 29.23 months vs 20.59 months (high NLR) (p = 0.019). Although demographics like male sex, smoking history, higher BMI and poor ECOG performance status had numerically increased the risk of developing IRAE, no statistical significance was noted. Conclusions: Overall results of our analysis are mostly consistent with the current literature on survival rates in Lung Cancer. IRAE may have a predictive role in survival, as we observed that patients with NSCLC developing IRAE had better survival rates. Ipilimumab-Nivolumab combination resulted in more IRAE than any other ICI. Pneumonitis was the most common IRAE among all patients receiving ICI. Also, Radiation-therapy increased the risk of developing IRAE. Our observation that steroid use in treating IRAE was associated with lower survival is concerning. This may be due to higher grade IRAE/toxicities and possible decreased ICI effectiveness. Regardless of IRAE, low pretreatment NLR resulted in better survival rates. The role of pretreatment NLR as a potential prognostic tool to assess survival outcomes requires validation in a randomized clinical trial.
Study of microwave ablation in patients with unresectable soft tissue sarcoma.
Authors: Yao Weitao, Xinhui Du
Journal: Journal of Clinical Oncology (2023)

e23545 Background: Currently, the main treatment for soft tissue sarcoma is a combination of radiotherapy, chemotherapy and complete surgical resection. However, there is no ideal method for soft tissue sarcoma after multiple recurrences, large tumours, insensitivity to radiotherapy or failure of down grade therapy. Microwave ablation is one of the main techniques for tumour thermal therapy, but its use in soft tissue sarcoma is not yet widespread. The aim of this study was to investigate the safety and efficacy of microwave ablation in refractory soft tissue sarcoma. Methods: Fourteen eligible patients with refractory soft tissue sarcoma were treated with local anaesthesia, multi-point intra-tumour needle placement under ultrasound guidance and local radiofrequency ablation (20-40 J, 2-5 minutes). For tumours larger than 5 cm in diameter, repeat ablation can be performed after 3-4 weeks. Of the 14 patients, 8 were male and 6 were female, with a mean age of 58.91 years. There were 4 cases of myxofibrosarcoma, 3 cases of dedifferentiated liposarcoma, 2 cases of malignant nerve sheath tumour, 2 cases of clear cell sarcoma and 3 cases of other sarcomas. Tumours were located in the trunk in 7 cases, in the upper limbs in 3 cases and in the lower limbs in 4 cases. Of these, 5 patients had two operations and 9 patients had three or more operations. Four cases had received first-line therapy, five cases had received second-line therapy, and five cases had received third-line therapy or more. Postoperative pain relief and wound complications were recorded. MRI was performed regularly to assess tumour shrinkage. Results: Post-operatively, all patients experienced a significant reduction in local swelling and pain. Post-operative imaging showed partial response (PR) in 11 cases and stable disease (SD) in 3 cases. The overall response rate (ORR) was 78.57%. Progression-free survival (PFS) ranged from 2-18 months with a median of 5.82 months. Complications included tumour ulceration in 2 cases, skin burns with necrosis in 2 cases and postoperative fever in 5 cases. Conclusions: For soft tissue sarcomas that cannot be removed by surgery, where tumour growth is slow and insensitive to radio/chemotherapy, local microwave ablation can achieve tumour shrinkage and reduce patient symptoms such as local swelling and pain. It is an effective treatment option for some specific sarcoma patients.
Will we have a match? Observations from decision making conversations between hematologists and White and Black patients considering allogeneic stem cell transplant.
Authors: Thorunn Halldora Thordardottir, Rachel Rodenbach, Toby Christopher Campbell
Journal: Journal of Clinical Oncology (2023)

12133 Background: Allogeneic stem cell transplant (alloSCT) is the only treatment associated with cure for high-risk myelodysplastic syndrome (MDS), but carries substantial risks. One routinely mentioned concern is donor source. While white patients have an 80% chance of finding an unrelated fully matched donor, Black patients have among the lowest chance at 30%. The aim of this secondary analysis, from a telemedicine study assessing how hematologists engage in shared decision making with patients considering alloSCT, is to analyze how hematologists navigate discussions about donor concerns related to the apparent race of the patient. Methods: This is a qualitative analysis of transcribed video-recorded virtual encounters. We recruited US hematologists who perform alloSCT and randomized them to meet with a patient actor of Black or white race. The hematologists conducted a new patient encounter with the actors who were trained to portray the same 67 year old man with newly diagnosed high-risk MDS referred for specialty consultation to discuss treatment options. The patient character had multiple healthy siblings and children. Results: Transcripts from a total of 33 hematologists were available at the time of analysis (61% male, 30% non-white, mean age 46 +/- 11 years). Hematologists spent varying amounts of time discussing the concept of transplant donation. While some used complex language to describe matching and HLA tissue markers, others used simplified terms of finding a donor with “an immune system that’s similar to your own,” to eradicate foreign MDS cells and avoid attack on healthy cells. The majority emphasized searching for a donor among siblings, given the highest likelihood of matching. Conversations with the white actor included reassurance of finding a fully matched donor, whether through family or the international registry. Hematologists frequently disclosed the highest chance of success for people of European ancestry. While hematologists mentioned the registry in conversations with the Black actor, they rarely disclosed the lower chance of finding a fully matched unrelated donor. Instead they reassured that with better technology haploidentical match could be an option through donation from their child, “with as favorable outcomes.” Some gave the Black actor an overestimation of finding a fully matched donor through the registry. Non-white hematologists more frequently acknowledged the concept of race in stem cell donation. Conclusions: Hematologists use multiple strategies to help patients understand the donor process. They reveal to white patients the high likelihood of finding a fully matched donor while appearing to avoid discussing the lower odds for a Black patient.
Fertility post immune checkpoint blockade.
Authors: Martinique Ogle, Emily Harrold, Erin O'Brien, Jill A. Weiss, Amin Yaqubie, Jenna Cohen Sinopoli, Michael A. Postow, Andrea Cercek
Journal: Journal of Clinical Oncology (2023)

12014 Background: Immune checkpoint blockade (ICB) is radically altering the treatment paradigm for a wide range of malignancies. Consequently, the proportion of ICB exposed pts will expand and the impact of ICB on fertility is of increasing importance. We sought to evaluate fertility outcomes post ICB exposure at our institution. Methods: Pts &lt; 45 years old post ≥ 1 cycles of ICB at MSK who consented to the MSK-IMPACT protocol (NCT01775072) were screened for eligibility (n = 537). Pts in receipt of prior cytotoxic chemotherapy or tyrosine kinase, BRAF or MEK inhibitors were excluded. 96 eligible pts were emailed a 28-question survey; 65% were followed up by phone. Results: 50/96 pts responded to the survey, male to female ratio was 27:23. 5 pts were excluded from final analysis due to additional systemic agent use pre-conception. Median age at ICB exposure was 35 (range 19-44). 53% (25/45) of pts received ICB in the metastatic setting. 40% (17/42) of pts received fertility counseling pre-ICB use. There was no statistically significant difference between rates of fertility counseling in metastatic vs non-metastatic settings (p = 0.14). 7 pts (14%) conceived and 2 pts (4%) are currently trying to conceive children post ICB. 4 pts (3 female, 1 male) conceived children with reproductive technology. 3/4 pts used sperm or embryos frozen prior to ICB and IVF leading to successful pregnancies, 2 of which are currently ongoing. One patient froze embryos 6 months after 2 years of PD1 inhibitor (PD1i) monotherapy and embryo implantation led to a currently ongoing pregnancy. Notably this pt developed hypothyroidism with ICB use, controlled with levothyroxine, and has remained euthyroid during pregnancy to date. 3 pts (2 female, 1 male) receiving single agent PD1i in the localized setting conceived naturally at 2 yrs, 9 months and 2 months respectively post ICB. 4/8 pregnancies are currently ongoing without reported immunological complications. 3 deliveries have resulted in 4 children (including 1 set of twins). 1 of these pts had a 1 st trimester miscarriage of unclear cause followed by successful pregnancy complicated by gestational diabetes. First pregnancies occurred a median of 1 year post ICB (range 2-24 months). No autoimmune conditions in progeny were reported. Conclusions: Successful conception occurred both naturally and with reproductive assistance technologies post ICB. Most pts did not receive fertility counseling pre-ICB use, possibly reflective of nascent appreciation of complete and durable ICB responses. There were no definite adverse immunological complications reported in pregnancy or progeny of these pts. As ICB indications expand prospective evaluation of ICB impact on fertility in pts desirous of a family is critical and consequently we are integrating longitudinal fertility analysis in neoadjuvant ICB protocols. [Table: see text]
Influence of widely targeted quantitative lipidomics on plasma lipid predictors and pathway dysregulation for nasopharyngeal carcinoma.
Authors: Xi Chen, Xiang Guo, Xing Lv
Journal: Journal of Clinical Oncology (2023)

6030 Background: Dysregulation of lipid metabolism is closely associated with cancer progression. We aimed to establish a prognostic model to predict distant metastasis-free survival (DMFS) in patients with locoregionally advanced nasopharyngeal carcinoma (NPC), based on widely targeted quantitative lipidomics. Methods: We measured and quantified the plasma lipid profiles of 179 patients with NPC using widely targeted quantitative lipidomics. Then, patients were randomly split into the training (125 patients, 69.8%) and validation (54 patients, 30.2%) sets. To identify distant metastasis-associated lipids, univariate Cox regression was applied to the training set ( p&lt; 0.05). We employed a deep survival method called DeepSurv to develop our proposed model based on significant lipid species ( p&lt; 0.01) and clinical biomarkers to predict DMFS. Concordance index and receiver operating curve analyses were performed to assess model effectiveness. We also explored the potential role of lipid alterations in the prognosis of NPC. Results: A total of 665 plasma endogenous lipid species consisting of 27 lipid classes and subclasses from 179 patients with NPC were annotated in lipidomics analysis. Forty lipids were recognized as distant metastasis-associated ( p&lt; 0.05) by univariate Cox regression. The concordance indices of our proposed model were 0.764 (95% confidence interval (CI), 0.682–0.846) and 0.760 (95% CI, 0.649–0.871) in the training and validation sets, respectively. We also calculated the C-index values of the baseline survival model based only on clinical biomarkers, with 0.718 (95% CI, 0.591–0.845) and 0.672 (95% CI, 0.511–0.833) being detected in the training and validation sets, respectively, indicating the outstanding predictive performance of lipid biomarkers. High-risk patients had poorer 5-year DMFS compared with low-risk patients (Hazard ratio, 26.18; 95% CI, 3.52–194.80; p&lt; 0.0001). Moreover, the six lipids were significantly correlated with immunity- and inflammation-associated biomarkers and were mainly enriched in metabolic pathways. Conclusions: Widely targeted quantitative lipidomics reveals plasma lipid predictors and pathway dysregulation for locoregionally advanced NPC, the prognostic model based on that demonstrated superior performance in predicting metastasis in NPC patients.
Durable clinical outcomes in patients (pts) with advanced melanoma and progression-free survival (PFS) ≥3y on nivolumab (NIVO) ± ipilimumab (IPI) or IPI in checkmate 067.
Authors: F. Stephen Hodi, Vanna Chiarion-Sileni, Rene Gonzalez, Jean-Jacques Grob, Piotr Rutkowski, Christopher D. Lao, Charles Lance Cowey, Dirk Schadendorf, John Wagstaff, Reinhard Dummer, Paola Queirolo, Michael Smylie, Marcus O. Butler, Andrew Graham Hill, Ivan Marquez-Rodas, Corey Ritchings, Leon A. Sakkal, Peter Wang, Jedd D. Wolchok, James Larkin
Journal: Journal of Clinical Oncology (2023)

9542 Background: NIVO + IPI has demonstrated durable clinical benefit at 7.5 y in pts with advanced melanoma in the phase 3 CheckMate 067 study. PFS curves plateaued at ~3 y in this study, suggesting that being alive and progression-free for ≥ 3 y (PFS ≥ 3y) may be a good surrogate for long-term clinical benefit. We conducted analyses to quantify this association. Methods: Pts with treatment (tx)-naive, unresectable stage III/IV melanoma (stratified by PD-L1 expression, BRAF mutation status, and metastasis stage) received NIVO 1 mg/kg + IPI 3 mg/kg for 4 doses Q3W, followed by NIVO 3 mg/kg Q2W (n = 314); NIVO 3 mg/kg Q2W + placebo (n = 316); or IPI 3 mg/kg Q3W for 4 doses + placebo (n = 315) until progression or unacceptable toxicity. Exploratory post hoc analysis was performed in pts with PFS ≥ 3y. Results: In the NIVO + IPI, NIVO, and IPI arms, respectively, 99 (32%), 78 (25%), and 21 (7%) pts had PFS ≥ 3y. Objective response rates (ORRs) in these pts were ≥ 95% (table). The majority of responses were complete responses (CRs; table); in almost all pts with partial responses (PRs) on NIVO + IPI or NIVO, target-lesion size decreased by ≥ 50%. At 7.5 y of follow-up among pts alive and progression-free at 3 y, PFS rates were ≥ 68%, overall survival (OS) rates were ≥ 85%, and melanoma-specific survival (MSS) rates were ≥ 95% in the 3 tx groups (table). Among pts in this group who died after 3 y on study, the majority of deaths were unrelated to disease (table). The majority of pts with PFS ≥ 3y who were alive and in follow-up were tx-free at the 7.5-y data cutoff (77/84, 57/64, and 13/16). Pts who received NIVO + IPI were off tx (median) for 75.5 mo (NIVO, 55.7 mo; IPI, 59.2 mo). Among pts with PFS ≥ 3y in the 3 tx groups, 4%, 5%, and 19% received subsequent systemic tx (table). No new safety signals were observed in pts with PFS ≥ 3y. Conclusions: This exploratory post hoc analysis suggested that PFS ≥ 3y may be a good surrogate for long-term MSS with NIVO + IPI or NIVO, with very few occurrences of progression or death due to melanoma in this population through 7.5 y. Most pts were tx-free without having received subsequent systemic tx after demonstrating PFS ≥ 3y. Further study of pts with PFS ≥ 3y may allow the burden of imaging and follow-up visits to be reduced in this group. Clinical trial information: NCT01844505 . [Table: see text]
Impact of antibiotics on survival outcomes and risk of gastritis/colitis in patients with advanced-stage melanoma receiving anti-PD-1 therapy.
Authors: Shannon Bailey, Thomas Havighurst, Vincent Pozorski, Yusuf Mohamoud, Dahlia Tesfamichael, Lindsey Jung, Elizabeth N. Dow-Hillgartner, Vincent T. Ma
Journal: Journal of Clinical Oncology (2023)

e21543 Background: Immune checkpoint inhibitors (ICIs), specifically anti-PD-1 therapy, have improved survival in advanced-stage melanoma patients compared to previous treatment options. A healthy gut microbiome has been associated with a positive response to ICIs. Antibiotics are known to disrupt the gut microbiome and may have immune-modulatory effects within the tumor microenvironment. Studies have demonstrated a negative impact on survival with any antibiotic use during ICI treatment. Less information is known regarding the impact of spectrum of activity or antibiotic timing on survival and risk of ICI-associated gastritis/colitis. Methods: We conducted a single-center, retrospective review of advanced-stage melanoma patients treated with anti-PD-1-based therapy (ipilimumab/nivolumab or anti-PD-1 monotherapy) between 2014-2022. Multiple clinicopathologic variables including antibiotic use, survival outcomes, and development of colitis and/or gastritis were assessed. Antibiotic spectrum of activity was divided into two groups: with anaerobic coverage and without anaerobic coverage. Antibiotic timing was assessed as patients who received antibiotics within 30-days prior to starting ICI and/or during treatment. Univariate and multivariate analyses on PFS and OS were performed using Cox proportional hazard models. Logistic regression models were used to assess risk of gastritis and/or colitis. Multivariate analyses accounted for age, gender, melanoma primary type, BRAF mutation status, presence of brain or liver metastases, and pre-treatment LDH levels. Results: A total of 214 patients were analyzed. Multivariate analysis demonstrated any antibiotic exposure during anti-PD-1 therapy was associated with improved OS [HR 0.500, 95% CI 0.303–0.826, p = 0.007]. Although not statistically significant, there was a trend towards worse OS in patients who received antibiotic therapy 30-days prior to ICI therapy [HR 1.726, 95% CI 0.994-2.995, p = 0.052]. Use of antibiotics without anaerobic coverage was associated with improved PFS [HR 0.462, 95% CI 0.273–0.782, p = 0.004] and OS [HR 0.399, 95% CI 0.200–0.789, p = 0.009]. Antibiotic exposure 30-days prior to initiating anti-PD-1 therapy increased the risk of developing gastritis and/or colitis [OR 1.990, 95% CI 0.744–2.651, p = 0.043]. Conclusions: Antibiotic timing and spectrum of activity may be predictive of survival outcomes and risk of gastritis/colitis in anti-PD-1-treated patients with advanced-stage melanoma. Unlike previous studies, we found improved survival in patients receiving antibiotics during treatment and in those receiving antibiotics without anaerobic coverage. Our results demonstrate the need to further investigate specific antibiotic agents as well as antibiotic timing and their clinical impact on patients receiving ICI treatment.
Clinical outcomes among patients with advanced non-small cell lung cancer who received targeted therapy in a real-world setting.
Authors: Mo Yang, Joanna P. MacEwan, Sai Sriteja Boppudi, Monica McClain, Richard O'Hara, Frank Liu, Paul K. Paik
Journal: Journal of Clinical Oncology (2023)

9051 Background: In the past decade, therapies targeting EGFR, KRAS, ALK, ROS1, BRAF, NTRK, MET, RET, HER2 and PD-L1 were approved and recommended by National Comprehensive Cancer Network (NCCN) for use in advanced non-small cell lung cancer (aNSCLC). This study compared real-world clinical outcomes in biomarker positive patients with aNSCLC who received treatments based on the NCCN NSCLC Guidelines (v5.2021) versus other therapies in the US. Methods: This is a retrospective cohort study of patients with aNSCLC using the TEMPUS oncology dataset. Patients were included if they were diagnosed with stage IIIB-IV NSCLC (index date) between 1/1/2012 and 12/31/2020, ≥18 years of age at index, were biomarker (i.e., EGFR, KRAS, ALK, ROS1, BRAF, NTRK, MET, RET, or PD-L1) positive, and received at least one line of treatment. Patients were stratified by NCCN recommended treatment (v5.2021) receipt anytime following aNSCLC diagnosis. Median overall survival (mOS), progression free survival (mPFS), and time to next treatment (mTTNT) were evaluated by treatment group using Kaplan Meier analysis. Patient demographic and clinical characteristics were evaluated as potential predictors of receipt of NCCN recommended therapy. Results: Of the 2,158 biomarker positive patients who met study criteria, 55.7% (N=1,201) received NCCN recommended treatment. PDL1 (38.0%), EGFR (32.2%), and/or KRAS (30.3%) were the most common over-expressions/mutations. Biomarker positive patients with aNSCLC treated with NCCN recommended treatment (N=1,201) in any line had significantly longer mOS (24.7mo, 95% CI: 22.5–27.6) than those treated with non-recommended treatment (N=957, 19.8mo, 95% CI: 17.5–22.6) (p&lt;0.001). Biomarker positive patients with aNSCLC treated with NCCN recommended treatment also had significantly longer mPFS (8.5mo, 95% CI: 7.9–9.0) and mTTNT (20.6mo, 95% CI:19.3–23.7) than those treated with non-recommended treatment (4.9mo, 95% CI: 4.5–5.4) and (11.0mo, 95% CI: 10.0–12.7), respectively (both p&lt;0.001). Never smokers (vs current smokers), patients of unknown or other race (vs whites), and patients who received 2 or more lines of treatment (vs 1) were more likely to receive NCCN recommended treatment and those with squamous or other/unknown histology (vs non-squamous) or missing ECOG scores (vs ECOG 0) were less likely to receive NCCN recommended treatment. Conclusions: In this study, biomarker positive patients with aNSCLC who received NCCN recommended treatment had significantly longer mOS, mPFS, and mTTNT than those who were treated with non-recommended regimens. Following the recommendations of the NCCN NSCLC Panel improves real-world clinical outcomes among biomarker positive patients with aNSCLC. Meanwhile, some biomarker positive patients—including current smokers and those with squamous cell histology—were less likely to receive targeted treatments.